γ-secretase

The γ-secretases are intramembrane cleaving protein complexes responsible for the generation of amyloid β (Aβ) from the amyloid precursor protein (APP). Apart from presenilins (PSEN) , a mature and active γ-secretase complex consists of three additional subunits: Nicastrin (Nct), PSEN enhancer 2 (Pen-2), and either anterior pharynx 1 (APH-1) A or B. The γ-secretase complexes proteolyse type 1 transmembrane proteins, among them the APP, the Notch receptors and ligands, the Erb4 receptor and N-Cadherin.

Inhibition of γ-secretase with DAPT significantly reduced the production of extracellular Aβ38, Aβ40, and Aβ42 in neurons of all genotypes.

Compounds that inhibit or modulate γ-secretase can be considered as a potential therapeutics for AD because their use appears to be a rational strategy to prevent senile plaque (SP) formations.